Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels.
The low selectivity of Kv1 peptide inhibitors for specific isoforms makes them poor candidates for the development of theraputics. Using combined approaches, we showed that the Kv1 turret is the critical determinant for ADWX-1 peptide inhibitor selectivity of Kv1.3 over Kv1.1. Mutation of Kv1.1 turret residues to match the sequence of Kv1.3 lead to increased inhibition of Kv1.1 activity. These studies may lead to improvements in peptide inhibitor drug development.
Yin
Shi-Jin
SJ
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Jiang
Ling
L
Yi
Hong
H
Han
Song
S
Yang
Dai-Wen
DW
Liu
Mai-Li
ML
Liu
Hui
H
Cao
Zhi-Jian
ZJ
Wu
Ying-Liang
YL
Li
Wen-Xin
WX
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D003198:Computer Simulation; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006860:Hydrogen Bonding; D051662:Kv1.1 Potassium Channel / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D004220:Disulfides; D051664:Kv1.3 Potassium Channel; D009842:Oligopeptides; D026902:Potassium Channel Blockers; D051662:Kv1.1 Potassium Channel